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Systematic (IUPAC) name
Clinical data
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
Half-life 1.5-4 hours
CAS number 24526-64-5 N
ATC code N06AX04
PubChem CID 4528
DrugBank DB04821
ChemSpider 4371 YesY
ChEBI CHEBI:116225 YesY
Chemical data
Formula C16H18N2 
Mol. mass 238.328 g/mol
 N (what is this?)  (verify)

Nomifensine (Merital, Alival) is a norepinephrine-dopamine reuptake inhibitor developed by a team at Hoechst AG in the 1960s.[1] The drug was test marketed in the United States by Hoechst AG (now Sanofi-Aventis), i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters.[2] This is a mechanism of action shared by some recreational drugs like cocaine and the medication, Tametraline(see DRI). Research showed that the (S) isomer is responsible for activity.[3]

Nomifensine was investigated for use as an antidepressant in the 1970s, and was found to be a useful antidepressant at doses of 50–225 mg per day, both motivating and anxiolytic. There were relatively few adverse effects (mainly dry mouth, headache, nausea), the drug was not sedating, did not interact significantly with alcohol and lacked anticholinergic effects. No withdrawal symptoms were seen after 6 months treatment. The drug was however considered not suitable for agitated patients as it presumably made agitation worse.[4][5]

Some case reports in the 1980s suggested that there was potential for psychological dependence on nomifensine, typically in patients with a history of stimulant addiction, or when the drug was used in very high doses (400–600 mg per day).[6]

In a 1989 study it has been investigated for use in treating adult ADHD and proven successful.[7] In a 1977 study it has not proven of benefit in advanced parkinsonism, except for depression associated with the parkinsonism.[8]

Due to the risk of a risk of haemolytic anaemia, the U.S. Food and Drug Administration (FDA) withdrew approval for nomifensine on March 20, 1992. Nomifensine has subsequently been withdrawn from the Canadian and UK markets as well.[9] Some deaths were linked to immunohaemolytic anemia caused by this compound although the mechanism remained unclear.[10]

In 2012 structure–affinity relationship data (compare SAR) were published.[11]


Nomifensine synthesis:[12]

See also[edit]


  1. ^ US patent 3577424, "4-Phenyl-8-Amino Tetrahydroisoquinolines", issued 1971-05-04, assigned to Farbwerke Hoechst 
  2. ^ Brogden, R. N.; Heel, R. C.; Speight, T. M.; Avery, G. S. (1979). "Nomifensine: A Review of its Pharmacological Properties and Therapeutic Efficacy in Depressive Illness". Drugs 18 (1): 1–24. doi:10.2165/00003495-197918010-00001. PMID 477572.  edit
  3. ^ 'Chirality and Biological Activity of Drugs' page 138
  4. ^ Habermann, W. (1977). "A Review of Controlled Studies with Nomifensine, Performed Outside the UK". British Journal of Clinical Pharmacology 4 (Suppl 2): 237S–241S. doi:10.1111/j.1365-2125.1977.tb05759.x. PMC 1429098. PMID 334230.  edit
  5. ^ Yakabow, A. L.; Hardiman, S.; Nash, R. J. (1984). "An Overview of Side Effects and long-term Experience with Nomifensine from United States Clinical Trials". The Journal of Clinical Psychiatry 45 (4 Pt 2): 96–101. PMID 6370985.  edit
  6. ^ Böning, J.; Fuchs, G. (2008). "Nomifensine and Psychological Dependence - a Case Report". Pharmacopsychiatry 19 (5): 386–388. doi:10.1055/s-2007-1017275. PMID 3774872.  edit
  7. ^ Shekim, W. O.; Masterson, A.; Cantwell, D. P.; Hanna, G. L.; McCracken, J. T. (1989). "Nomifensine Maleate in Adult Attention Deficit Disorder". The Journal of Nervous and Mental Disease 177 (5): 296–299. doi:10.1097/00005053-198905000-00008. PMID 2651559.  edit
  8. ^ Bedard, P.; Parkes, J. D.; Marsden, C. D. (1977). "Nomifensine in Parkinson's Disease". British Journal of Clinical Pharmacology 4 (Suppl 2): 187S–190S. doi:10.1111/j.1365-2125.1977.tb05751.x. PMC 1429119. PMID 334223.  edit
  9. ^ "Nomifensine DB04821". 
  10. ^ Galbaud du Fort, G. (1988). "Hematologic toxicity of antidepressive agents" [Hematologic Toxicity of Antidepressive Agents]. L'Encephale (in French) 14 (4): 307–318. PMID 3058454.  edit
  11. ^ Pechulis AD et al (2012): "4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors", Bioorg. Med. Chem. Lett., 7219. PMID 23084899
  12. ^ Zara-Kaczian, E.; Gyorgy, L.; Deak, G.; Seregi, A.; Doda, M. (1986). "Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property". Journal of Medicinal Chemistry 29 (7): 1189. doi:10.1021/jm00157a012.  edit